Skip to main content
. Author manuscript; available in PMC: 2021 Oct 18.
Published in final edited form as: Ann Lymphoma. 2020 Sep 30;4:7. doi: 10.21037/aol-20-20

Figure 1. Driver pathways in the pathogenesis of marginal zone lymphoma.

Figure 1

The NF-κB pathway plays a critical role in the development of MZL and can be activated by various mechanisms. BCR signaling dysregulation is a hallmark of MZL and can mimic antigen dependent BCR activation. Upon activation of BCR, SRC family proteins (i.e., LYN) phosphorylate the ITAMs of CD79A/B, which signals the recruitment of SYK in order to augment signaling. LYN is also able to activate and recruit PI3K pathway. BTK is then activated by LYN and SYK kinases, and in turn phosphorylates PLCγ2, leading to the proteolysis of PIP2 into DAG and IP3, triggering an influx of calcium into the cytoplasm that goes on to activate PKCβ. PKCβ phosphorylates CARD11, which then goes on to form the CBM complex with BCL10 and MALT1, eventually leading to downstream NF-κB activation. MYD88 L265P mutations leads to lymphomagenesis through activation of the TLR and IL1R pathways independent of ligand stimulation. Additional mutations and overexpression in other proteins involved in BCR signaling and interrelated pathways include CARD11, TNFAIP3, SYK, NOTCH2.